The range of brain capillary permeability measurements has been extended by use of the arterial integral method. A 5 isotope combination permits the simultaneous measurement of cerebral blood flow, vascular volume, and the permeability of brain capillaries to 3 compounds of different molecular size. A new quantitative autoradiographic technique using 14C-alpha-aminoisobutyric acid (AIB) was developed which can measure up to a 100-fold increase in capillary permeability in focal brain regions 100 microns in diameter; tumors X-irradiation, ischemia, and the freeze lesion were studied. The delayed effects of X-irradiation begin with focal changes in the permeability of the capillaries and progress to graded size opening of the blood-brain barrier. Cerebral edema may be generated through osmotic as well as hydrostatic pressure gradients across the capillaries; bulk flow of edema fluid from a lesion site along known anatomic pathways to specific sites remote from the lesion was supported. Low energy microwave irradiation did not alter capillary permeability or cerebral blood flow. Metrizamide was found to cross brain capillaries very slowly; metrizamide does diffuse from CSF into brain tissue but does not appreciably enter normal brain cells. Spirohydantoin mustard crosses brain capillaries and enters brain cells very rapidly.